This program is a continuation of our studies of the effects of androgens and antiandrogens in the regulation of prostatic growth and is composed of two major parts: I. We have recently isolated and characterized a new structural component of the nucleus, termed the nuclear protein matrix. We have evidence that this matrix is associated with the component of DNA in the nucleus that is rapidly labeled during DNA synthesis and appears to be the site of DNA replication. We have isolated the nuclear protein matrix from prostatic tissue and propose studies to characterize this structure and its possible function during various phases of androgen-induced growth in sex-accessory tissues. This will be a continuation of our studies of the regulation of androgens and antiandrogens in relation to biochemical events accompanying DNA synthesis in hormone sensitive tissues. II. Antiandrogens are receiving increasing attention as new therapeutic agents in the treatment of human benign prostatic hypertrophy and prostatic adenocarcinoma. We have developed a new model for testing the potency and mechanism of action of antiandrogens which involves the effects of these agents on prostatic DNA synthesis occurring at 72 hours following androgen administration to castrate rats. In addition, we will test a series of these antiandrogens for their ability to affect nuclear uptake of androgens; affect testosterone synthesis in a rabbit testes perfusate system; their possible inhibitory properties on certain enzymes that are involved in steroid biotransformation with particular emphasis on the ketosteroid isomerase and androgen glucuronide formation. We have also synthesized and iodinated antiandrogen derivative that can be radiolabeled and will use this analogue to determine subcellular uptake of an antiandrogen. BIBLIOGRAPHIC REFERENCES: Berezney, R. and D. S. Coffey. Association of Newly Replicated DNA with the Nuclear Protein Matrix. J. Cell Biol. 67, 29a, 1975. (Abstract). Heston, W.D.W., A. M. Benson, C. E. Chubb, D. S. Coffey, L. L. Ewing, and P. Talalay. Differentiation Between Two Types of Antiandrogenic Activity Among Structurally Related Steroids. International Symposium on Androgens and Antiandrogens. Milan (Italy), April 26-28, 1976. (Abstract).